Skip to main content
SpringerLink
Log in

Primary sclerosing cholangitis: Diagnosis and management

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease caused by progressive inflammatory destruction of intrahepatic and extrahepatic bile ducts, and ultimately cirrhosis. PSC occurs primarily in patients with underlying ulcerative colitis and affects primarily young to middle-aged men. PSC is believed to be an autoimmune disease mediated by immune dysregulation in patients with genetic susceptibility. One possible mechanism for the development of PSC is the homing of memory lymphocytes to the biliary tract. Cholangiography is the gold standard for diagnosis of PSC. The typical radiologic findings include multifocal strictures and dilation involving the intrahepatic or extrahepatic biliary tract, or both. Although no medical therapy has proved beneficial, a variety of agents have been tested, some of which appear promising and deserve further study. Highdose ursodeoxycholic acid may have benefit in slowing disease progression; a multicenter placebo-controlled trial is ongoing. Liver transplantation is a good option for patients with advanced PSC, although the disease can recur after successful transplantation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Boberg KM, Aadland E, Jahnsen J, et al.: Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol 1998, 33:99–103.

    Article  PubMed  CAS  Google Scholar 

  2. Bambha K, Kim WR, Talwalkar J, et al.: Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology 2003, 125:1364–1369.

    Article  PubMed  Google Scholar 

  3. Kingham JG, Kochar N, Gravenor MB: Incidence, clinical patterns, and outcomes of primary sclerosing cholangitis in South Wales, United Kingdom. Gastroenterology 2004, 126:1929–1930.

    Article  PubMed  Google Scholar 

  4. Bergquist A, Lindberg G, Saarinen S, et al.: Increased prevalence of primary sclerosing cholangitis among firstdegree relatives. J Hepatol 2005, 42:252–256. These data support the hypothesis that genetic factors are important for development of PSC.

    Article  PubMed  Google Scholar 

  5. Lawson A, West J, Aithal GP, et al.: Autoimmune cholestatic liver disease in people with coeliac disease: a population-based study of their association. Aliment Pharmacol Ther 2005, 21:401–405.

    Article  PubMed  CAS  Google Scholar 

  6. Talwalkar JA, Lindor KD: Primary sclerosing cholangitis. Inflamm Bowel Dis 2005, 11:62–72.

    Article  PubMed  Google Scholar 

  7. Aoki CA, Bowlus CL, Gershwin ME: The immunobiology of primary sclerosing cholangitis. Autoimmun Rev 2005, 4:137–143.

    Article  PubMed  CAS  Google Scholar 

  8. Feldstein AE, Perrault J, El-Youssif M, et al.: Primary sclerosing cholangitis in children: a long-term follow-up study. Hepatology 2003, 38:210–217.

    Article  PubMed  Google Scholar 

  9. Nakazawa T, Ohara H, Sano H, et al.: Cholangiography can discriminate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis. Gastrointest Endosc 2004, 60:937–944.

    Article  PubMed  Google Scholar 

  10. Resnick D, Krinsky GA, Lavelle MT, et al.: Do patients with primary sclerosing cholangitis have a greater frequency of pancreatic abnormalities at MRI than patients with other liver diseases? J Comput Assist Tomogr 2002, 26:994–999.

    Article  PubMed  Google Scholar 

  11. Angulo P, Pearce DH, Johnson CD, et al.: Magnetic resonance cholangiography in patients with biliary disease: its role in primary sclerosing cholangitis. J Hepatol 2000, 33:520–527.

    Article  PubMed  CAS  Google Scholar 

  12. Textor HJ, Flacke S, Pauleit D, et al.: Three-dimensional magnetic resonance cholangiopancreatography with respiratory triggering in the diagnosis of primary sclerosing cholangitis: comparison with endoscopic retrograde cholangiography. Endoscopy 2002, 34:984–990.

    Article  PubMed  CAS  Google Scholar 

  13. Talwalkar JA, Angulo P, Johnson CD, et al.: Cost-minimization analysis of MRC versus ERCP for the diagnosis of primary sclerosing cholangitis. Hepatology 2004, 40:39–45.

    Article  PubMed  Google Scholar 

  14. Silva AC, Friese JL, Hara AK, et al.: MR cholangiopancreatography: improved ductal distention with intravenous morphine administration. Radiographics 2004, 24:677–687.

    Article  PubMed  Google Scholar 

  15. Macchi V, Floreani A, Marchesi P, et al.: Imaging of primary sclerosing cholangitis: preliminary results by two new non-invasive techniques. Dig Liver Dis 2004, 36:614–621.

    Article  PubMed  CAS  Google Scholar 

  16. Hirche TO, Russler J, Braden B, et al.: Sonographic detection of perihepatic lymphadenopathy is an indicator for primary sclerosing cholangitis in patients with inflammatory bowel disease. Int J Colorectal Dis 2004, 19:586–594.

    Article  PubMed  Google Scholar 

  17. Burak KW, Angulo P, Lindor KD: Is there a role for liver biopsy in primary sclerosing cholangitis? Am J Gastroenterol 2003, 98:1155–1158.

    Article  PubMed  Google Scholar 

  18. Angulo P, Maor-Kendler Y, Lindor KD: Small-duct primary sclerosing cholangitis: a long-term follow-up study. Hepatology 2002, 35:1494–1500.

    Article  PubMed  Google Scholar 

  19. Bjornsson E, Boberg KM, Cullen S, et al.: Patients with small duct primary sclerosing cholangitis have a favorable long term prognosis. Gut 2002, 51:731–735.

    Article  PubMed  CAS  Google Scholar 

  20. Kaya M, Angulo P, Lindor KD: Overlap of autoimmune hepatitis and primary sclerosing cholangitis: an evaluation of a modified scoring system. J Hepatol 2000, 33:537–42.

    Article  PubMed  CAS  Google Scholar 

  21. GheorgheL, Iacob S, Gheorghe C, et al.: Frequency and predictive factors for overlap syndrome between autoimmune hepatitis and primary cholestatic liver disease. Eur J Gastroenterol Hepatol 2004, 16:585–592. These authors identified the independent predictive factors associated with the diagnosis of overlap syndrome, which were young age, ANA seronegativity, and probable diagnosis according to the scoring system for AIH.

    Article  PubMed  Google Scholar 

  22. Floreani A, Rizzotto ER, Ferrara F, et al.: Clinical course and outcome of autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. Am J Gastroenterol 2005, 100:1516–1522.

    Article  PubMed  Google Scholar 

  23. Zein CO, Lindor KD, Angulo P: Prevalence and predictors of esophageal varices in patients with primary sclerosing cholangitis. Hepatology 2004, 39:204–210.

    Article  PubMed  Google Scholar 

  24. Bjornsson E, Simren M, Olsson R, et al.: Fatigue in patients with primary sclerosing cholangitis. Scand J Gastroenterol 2004, 39:961–8.

    Article  PubMed  CAS  Google Scholar 

  25. ter Borg PC, van Os E, van den Broek WW, et al.: Fluvoxamine for fatigue in primary biliary cirrhosis and primary sclerosing cholangitis: a randomised controlled trial [ISRCTN88246634]. BMC Gastroenterol 2004, 4:1–13.

    Article  CAS  Google Scholar 

  26. Epstein MP, Kaplan MM: A pilot study of etanercept in the treatment of primary sclerosing cholangitis. Dig Dis Sci 2004, 49:1–4.

    Article  PubMed  CAS  Google Scholar 

  27. Campbell MS, Lichtenstein GR, Rhim AD, et al.: Severity of liver disease does not predict osteopenia or low bone mineral density in primary sclerosing cholangitis. Liver Int 2005, 25:311–316.

    Article  PubMed  Google Scholar 

  28. Kaya M, Petersen BT, Angulo P, et al.: Balloon dilation compared to stenting of dominant strictures in primary sclerosing cholangitis. Am J Gastroenterol 2001, 96:1059–1066.

    Article  PubMed  CAS  Google Scholar 

  29. Bjornsson E, Lindqvist-Ottosson J, Asztely M, et al.: Dominant strictures in patients with primary sclerosing cholangitis. Am J Gastroenterol 2004, 99:502–508. This study demonstrated that cholestasis in patients with PSC does not seem to be related to the presence of dominant stricture, and that endoscopic therapy should not be routinely undertaken.

    Article  PubMed  Google Scholar 

  30. Stiehl A, Rudolph G, Kloters-Plachky P, et al.: Development of dominant bile duct stenoses in patients with primary sclerosing cholangitis treated with ursodeoxycholic acid: outcome after endoscopic treatment. J Hepatol 2002, 36:151–156.

    Article  PubMed  Google Scholar 

  31. Vuddagiri SK, France R, Kozarek R: Endoscopic therapy in primary sclerosing cholangitis (PSC): does the complication risk outweigh therapeutic benefit? [abstract]. Gastrointest Endosc 2004: 59:AB193.

    Article  Google Scholar 

  32. Burak K, Angulo P, Pasha TM, et al.: Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol 2004, 99:523–526.

    Article  PubMed  Google Scholar 

  33. BrandsaeterB, Isoniemi H, Broome U, et al.: Liver transplantation for primary sclerosing cholangitis, predictors and consequences of hepatobiliary malignancy. J Hepatol 2004, 40:815–822. This prospective study sought to determine predictors of hepatobiliary malignancy in PSC patients listed for liver transplantation that might add to our knowledge on how to handle these patients.

    Article  PubMed  CAS  Google Scholar 

  34. Levy C, Lymp J, Angulo P, et al.: The value of serum CA 19–9 in predicting cholangiocarcinomas in patients with primary sclerosing cholangitis. Dig Dis Sci 2005, 50:1734–1740.

    Article  PubMed  CAS  Google Scholar 

  35. Lindberg B, Arnelo U, Bergquist A, et al.: Diagnosis of biliary strictures in conjunction with endoscopic retrograde cholangiopancreaticography, with special reference to patients with primary sclerosing cholangitis. Endoscopy 2002, 34:909–916.

    Article  PubMed  CAS  Google Scholar 

  36. Koopmann J, Thuluvath PJ, Zahurak ML, et al.: Mac-2-binding protein is a diagnostic marker for biliary tract carcinoma. Cancer 2004, 101:1609–1615.

    Article  PubMed  CAS  Google Scholar 

  37. Berr F: Photodynamic therapy for cholangiocarcinoma. Semin Liver Dis 2004, 24:177–187.

    Article  PubMed  Google Scholar 

  38. Abu-Hamda EM, Baron TH: Endoscopic management of cholangiocarcinoma. Semin Liver Dis 2004, 24:165–175.

    Article  PubMed  Google Scholar 

  39. Buckles DC, Lindor KD, Larusso NF, et al.: In primary sclerosing cholangitis, gallbladder polyps are frequently malignant. Am J Gastroenterol 2002, 97:1138–1142.

    Article  PubMed  Google Scholar 

  40. Loftus EV Jr, Harewood GC, Loftus CG, et al.: PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut 2005, 54:91–96. Based on the clinical features and outcomes of IBD associated with PSC, PSC-IBD may represent a distinct IBD phenotype.

    Article  PubMed  Google Scholar 

  41. Pardi DS, Loftus EV Jr, Kremers WK, et al.: Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology 2003, 124:889–893.

    Article  PubMed  CAS  Google Scholar 

  42. Stahlberg D, Veress B, Tribukait B, et al.: Atrophy and neoplastic transformation of the ileal pouch mucosa in patients with ulcerative colitis and primary sclerosing cholangitis: a case control study. Dis Colon Rectum 2003, 46:770–778.

    Article  PubMed  Google Scholar 

  43. Vera A, Gunson BK, Ussatoff V, et al.: Colorectal cancer in patients with inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis. Transplantation 2003, 75:1983–1988.

    Article  PubMed  Google Scholar 

  44. Beuers U, Spengler U, Kruis W, et al.: Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial. Hepatology 1992, 16:707–714.

    Article  PubMed  CAS  Google Scholar 

  45. Stiehl A, Walker S, Stiehl L, et al.: Effect of ursodeoxycholic acid on liver and bile duct disease in primary sclerosing cholangitis. A 3-year pilot study with a placebo-controlled study period. J Hepatol 1994, 20:57–64.

    Article  PubMed  CAS  Google Scholar 

  46. Lindor KD: Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group. N Engl J Med 1997, 336:691–695.

    Article  PubMed  CAS  Google Scholar 

  47. van Hoogstraten HJ, Wolfhagen FH, van de Meeberg PC, et al.: Ursodeoxycholic acid therapy for primary sclerosing cholangitis: results of a 2-year randomized controlled trial to evaluate single versus multiple daily doses. J Hepatol 1998, 29:417–423.

    Article  PubMed  Google Scholar 

  48. Rost D, Rudolph G, Kloeters-Plachky P, et al.: Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis. Hepatology 2004, 40:693–698. If biliary enrichment of UDCA represents the decisive factor for its clinical effect, this study demonstrated that biliary enrichment of UDCA increases with increasing dose and reaches a plateau at 22 to 25 mg/kg with no increase of toxic hydrophobic bile acids.

    Article  PubMed  CAS  Google Scholar 

  49. Mitchell SA, Bansi DS, Hunt N, et al.: A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis. Gastroenterology 2001, 121:900–907.

    Article  PubMed  CAS  Google Scholar 

  50. Harnois DM, Angulo P, Jorgensen RA, et al.: High-dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis. Am J Gastroenterol 2001, 96:1558–1562.

    Article  PubMed  CAS  Google Scholar 

  51. Olsson RG, Boberg KM, Schaffalitzky de Muckadel O, et al.: Five year treatment with high dose UDCA in PSC [abstract]. J Hepatol 2004, 40:161.

    Article  Google Scholar 

  52. LaRusso NF, Wiesner RH, Ludwig J, et al.: Prospective trial of penicillamine in primary sclerosing cholangitis. Gastroenterology 1988, 95:1036–1042.

    PubMed  CAS  Google Scholar 

  53. Olsson R, Broome U, Danielsson A, et al.: Colchicine treatment of primary sclerosing cholangitis. Gastroenterology 1995, 108:1199–1203.

    Article  PubMed  CAS  Google Scholar 

  54. Knox TA, Kaplan MM: A double-blind controlled trial of oral-pulse methotrexate therapy in the treatment of primary sclerosing cholangitis. Gastroenterology 1994, 106:494–499.

    PubMed  CAS  Google Scholar 

  55. Sandborn WJ, Wiesner RH, Tremaine WJ, et al.: Ulcerative colitis disease activity following treatment of associated primary sclerosing cholangitis with cyclosporin. Gut 1993, 34:242–246.

    PubMed  CAS  Google Scholar 

  56. Vleggaar FP, van Buuren HR, van Berge HenegouwenGP, et al.: No beneficial effects of transdermal nicotine in patients with primary sclerosing cholangitis: results of a randomized double-blind placebo-controlled cross-over study. Eur J Gastroenterol Hepatol 2001, 13:171–175.

    Article  PubMed  CAS  Google Scholar 

  57. Bharucha AE, Jorgensen R, Lichtman SN, et al.: A pilot study of pentoxifylline for the treatment of primary sclerosing cholangitis. Am J Gastroenterol 2000, 95:2338–2342.

    Article  PubMed  CAS  Google Scholar 

  58. Angulo P, Jorgensen R, Keach J, et al.: Silymarin in the treatment of patients with primary sclerosing cholangitis. Gastroenterology 2001, 120(Suppl.1):A353.

    Article  Google Scholar 

  59. Angulo P, Bharucha AE, Jorgensen RA, et al.: Oral nicotine in treatment of primary sclerosing cholangitis: a pilot study. Dig Dis Sci 1999, 44:602–607.

    Article  PubMed  CAS  Google Scholar 

  60. Angulo P, MacCarty RL, Sylvestre PB, et al.: Pirfenidone in the treatment of primary sclerosing cholangitis. Dig Dis Sci 2002, 47:157–161.

    Article  PubMed  CAS  Google Scholar 

  61. van HoogstratenHJ, Vleggaar FP, Boland GJ, et al.: Budesonide or prednisone in combination with ursodeoxycholic acid in primary sclerosing cholangitis: a randomized double-blind pilot study. Belgian-Dutch PSC Study Group. Am J Gastroenterol 2000, 95:2015–2022.

    Article  PubMed  Google Scholar 

  62. Angulo P, Batts KP, Jorgensen RA, et al.: Oral budesonide in the treatment of primary sclerosing cholangitis. Am J Gastroenterol 2000, 95:2333–2337.

    Article  PubMed  CAS  Google Scholar 

  63. Duchini A, Younossi ZM, Saven A, et al.: An open-label pilot trial of cladibrine (2-cholordeoxyadenosine) in patients with primary sclerosing cholangitis. J Clin Gastroenterol 2000, 31:292–296.

    Article  PubMed  CAS  Google Scholar 

  64. Talwalkar JA, Angulo P, Keach JC, et al.: Mycophenolate mofetil for the treatment of primary biliary cirrhosis in patients with an incomplete response to ursodeoxycholic acid. J Clin Gastroenterol 2005, 39:168–171.

    Article  PubMed  CAS  Google Scholar 

  65. Chen W, Gluud C: Glucocorticosteroids for primary sclerosing cholangitis. Cochrane Database Syst Rev 2004, (3):CD004036.

  66. Van Thiel DH, Carroll P, Abu-Elmagd K, et al.: Tacrolimus (FK 506), a treatment for primary sclerosing cholangitis: results of an open-label preliminary trial. Am J Gastroenterol 1995, 90:455–459.

    PubMed  Google Scholar 

  67. Schramm C, Schirmacher P, Helmreich-Becker I, et al.: Combined therapy with azathioprine, prednisolone, and ursodiol in patients with primary sclerosing cholangitis. A case series. Ann Intern Med 1999, 131:943–946.

    PubMed  CAS  Google Scholar 

  68. Lindor KD, Wiesner RH, Colwell LJ, et al.: The combination of prednisone and colchicine in patients with primary sclerosing cholangitis. Am J Gastroenterol 1991, 86:57–61.

    PubMed  CAS  Google Scholar 

  69. Lindor KD, Jorgensen RA, Anderson ML, et al.: Ursodeoxycholic acid and methotrexate for primary sclerosing cholangitis: a pilot study. Am J Gastroenterol 1996, 91:511–515.

    PubMed  CAS  Google Scholar 

  70. Sterling RK, Salvatori JJ, Luketic VA, et al.: A prospective, randomized-controlled pilot study of ursodeoxycholic acid combined with mycophenolate mofetil in the treatment of primary sclerosing cholangitis. Aliment Pharmacol Ther 2004, 20:943–949.

    Article  PubMed  CAS  Google Scholar 

  71. Farkkila M, Karvonen AL, Nurmi H, et al.: Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: a randomized placebo-controlled trial. Hepatology 2004, 40:1379–1386.

    Article  PubMed  CAS  Google Scholar 

  72. Brandsaeter B, Friman S, Broome U, et al.: Outcome following liver transplantation for primary sclerosing cholangitis in the Nordic countries. Scand J Gastroenterol 2003, 38:1176–1183.

    Article  PubMed  CAS  Google Scholar 

  73. Vera A, Moledina S, Gunson B, et al.: Risk factors for recurrence of primary sclerosing cholangitis of liver allograft. Lancet 2002, 360:1943–1944.

    Article  PubMed  Google Scholar 

  74. Kugelmas M, Spiegelman P, Osgood MJ, et al.: Different immunosuppressive regimens and recurrence of primary sclerosing cholangitis after liver transplantation. Liver Transpl 2003, 9:727–732.

    Article  PubMed  Google Scholar 

  75. MaheshwariA, Yoo HY, Thuluvath PJ: Long-term outcome of liver transplantation in patients with PSC: a comparative analysis with PBC. Am J Gastroenterol 2004, 99:538–542. Based on this study using the UNOS database, the authors do not recommend preemptive liver transplantation for patients with PSC.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, 200 First Street, SW, 55905, Rochester, MN, USA

    Keith D. Lindor MD

Authors
  1. Phunchai Charatcharoenwitthaya MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keith D. Lindor MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keith D. Lindor MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Charatcharoenwitthaya, P., Lindor, K.D. Primary sclerosing cholangitis: Diagnosis and management. Curr Gastroenterol Rep 8, 75–82 (2006). https://doi.org/10.1007/s11894-006-0067-8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-006-0067-8

Keywords

Search

Navigation